Abstract
Fetal alveolar type II (fATII) epithelial cells were used to evaluate the role of signaling factors involved in oxidative stress-induced programmed cell death (PCD; apoptosis). Bcl-2, an antiapoptotic proto-oncogene, showed maximum abundance in hypoxia and mild reoxygenation, but declined thereafter. The Bcl-2 counterpart, Bax, which promotes PCD, displayed an increasing log arithmic profile with ascending ΔpO2 regimen, such that the ratio of Bcl-2/Bax decreased as pO2 increased. The expression of p53, a cell cycle regulator, paralleled Bax abundance. Pretreatment of fATII cells with L-buthionine-(S,R)-sulfoximine, an irreversible inhibitor of γ-glutamylcysteine synthetase, the rate-limiting enzyme in the biosynthesis of glutathione (GSH), enhanced Bax and p53 expression over Bcl-2. The GSH analogue, γ-glutamylcysteinyl-ethyl ester, down-regulated Bax/p53 abundance but restored that of Bcl-2, thereby increasing Bcl-2/Bax. The antioxidant and GSH precursor N-acetyl-L-cysteine favored Bcl-2 at the expense of Bax/p53, whereas pyrrolidine dithiocarbamate induced Bax against Bcl-2, with mild effect on p53. Sulfasalazine, a potent and specific inhibitor of NF-κB, induced Bax at the expense of Bcl-2, in a p53-dependent manner. We conclude that the differential expression of signaling factors involved in PCD in the alveolar epithelium is redox-sensitive and mediated, at least in part, by a negative feedback mechanism transduced by NF-κB. (C) 2000 Academic Press.
| Original language | English |
|---|---|
| Pages (from-to) | 257-267 |
| Number of pages | 11 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 271 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 29 Apr 2000 |
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Keywords
- Apoptosis
- Glutathione
- N-acetyl-L-cysteine
- NF-κB (RelA/p65)
- Pyrrolidine dithiocarbamate
- Redox equilibrium
- Sulfasalazine
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The Differential Expression of Apoptosis Factors in the Alveolar Epithelium Is Redox Sensitive and Requires NF-κB (RelA)-Selective Targeting. / Haddad, John J. E.; Land, Stephen C.
In: Biochemical and Biophysical Research Communications, Vol. 271, No. 1, 29.04.2000, p. 257-267.Research output: Contribution to journal › Article
TY - JOUR
T1 - The Differential Expression of Apoptosis Factors in the Alveolar Epithelium Is Redox Sensitive and Requires NF-κB (RelA)-Selective Targeting
AU - Haddad, John J. E.
AU - Land, Stephen C.
PY - 2000/4/29
Y1 - 2000/4/29
N2 - Fetal alveolar type II (fATII) epithelial cells were used to evaluate the role of signaling factors involved in oxidative stress-induced programmed cell death (PCD; apoptosis). Bcl-2, an antiapoptotic proto-oncogene, showed maximum abundance in hypoxia and mild reoxygenation, but declined thereafter. The Bcl-2 counterpart, Bax, which promotes PCD, displayed an increasing log arithmic profile with ascending ΔpO2 regimen, such that the ratio of Bcl-2/Bax decreased as pO2 increased. The expression of p53, a cell cycle regulator, paralleled Bax abundance. Pretreatment of fATII cells with L-buthionine-(S,R)-sulfoximine, an irreversible inhibitor of γ-glutamylcysteine synthetase, the rate-limiting enzyme in the biosynthesis of glutathione (GSH), enhanced Bax and p53 expression over Bcl-2. The GSH analogue, γ-glutamylcysteinyl-ethyl ester, down-regulated Bax/p53 abundance but restored that of Bcl-2, thereby increasing Bcl-2/Bax. The antioxidant and GSH precursor N-acetyl-L-cysteine favored Bcl-2 at the expense of Bax/p53, whereas pyrrolidine dithiocarbamate induced Bax against Bcl-2, with mild effect on p53. Sulfasalazine, a potent and specific inhibitor of NF-κB, induced Bax at the expense of Bcl-2, in a p53-dependent manner. We conclude that the differential expression of signaling factors involved in PCD in the alveolar epithelium is redox-sensitive and mediated, at least in part, by a negative feedback mechanism transduced by NF-κB. (C) 2000 Academic Press.
AB - Fetal alveolar type II (fATII) epithelial cells were used to evaluate the role of signaling factors involved in oxidative stress-induced programmed cell death (PCD; apoptosis). Bcl-2, an antiapoptotic proto-oncogene, showed maximum abundance in hypoxia and mild reoxygenation, but declined thereafter. The Bcl-2 counterpart, Bax, which promotes PCD, displayed an increasing log arithmic profile with ascending ΔpO2 regimen, such that the ratio of Bcl-2/Bax decreased as pO2 increased. The expression of p53, a cell cycle regulator, paralleled Bax abundance. Pretreatment of fATII cells with L-buthionine-(S,R)-sulfoximine, an irreversible inhibitor of γ-glutamylcysteine synthetase, the rate-limiting enzyme in the biosynthesis of glutathione (GSH), enhanced Bax and p53 expression over Bcl-2. The GSH analogue, γ-glutamylcysteinyl-ethyl ester, down-regulated Bax/p53 abundance but restored that of Bcl-2, thereby increasing Bcl-2/Bax. The antioxidant and GSH precursor N-acetyl-L-cysteine favored Bcl-2 at the expense of Bax/p53, whereas pyrrolidine dithiocarbamate induced Bax against Bcl-2, with mild effect on p53. Sulfasalazine, a potent and specific inhibitor of NF-κB, induced Bax at the expense of Bcl-2, in a p53-dependent manner. We conclude that the differential expression of signaling factors involved in PCD in the alveolar epithelium is redox-sensitive and mediated, at least in part, by a negative feedback mechanism transduced by NF-κB. (C) 2000 Academic Press.
KW - Apoptosis
KW - Glutathione
KW - N-acetyl-L-cysteine
KW - NF-κB (RelA/p65)
KW - Pyrrolidine dithiocarbamate
KW - Redox equilibrium
KW - Sulfasalazine
UR - http://www.scopus.com/inward/record.url?scp=0034728783&partnerID=8YFLogxK
U2 - 10.1006/bbrc.2000.2607
DO - 10.1006/bbrc.2000.2607
M3 - Article
C2 - 10777712
AN - SCOPUS:0034728783
VL - 271
SP - 257
EP - 267
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -